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EGFR wild type antagonizes EGFRvIII-mediated activation of Met in glioblastoma

Oncogene volume 34, pages 129–134 (2015)Cite this article

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Abstract

Epidermal growth factor receptor (EGFR)vIII is the most common EGFR mutant found in glioblastoma (GBM). EGFRvIII does not bind ligand, is highly oncogenic and is usually coexpressed with EGFR wild type (EGFRwt). EGFRvIII activates Met, and Met contributes to EGFRvIII-mediated oncogenicity and resistance to treatment. Here, we report that addition of EGF results in a rapid loss of EGFRvIII-driven Met phosphorylation in glioma cells. Met is associated with EGFRvIII in a physical complex. Addition of EGF results in a dissociation of the EGFRvIII–Met complex with a concomitant loss of Met phosphorylation. Consistent with the abrogation of Met activation, addition of EGF results in the inhibition of EGFRvIII-mediated resistance to chemotherapy. Thus, our study suggests that ligand in the milieu of EGFRvIII-expressing GBM cells is likely to influence the EGFRvIII–Met interaction and resistance to treatment, and highlights a novel antagonistic interaction between EGFRwt and EGFRvIII in glioma cells.

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Acknowledgements

This work was supported in part by NIH grant RO1NS062080 to AAH and by RO1 CA139217 to DAB. SB is supported by grants from the National Institutes of Health (RO1 CA149461), National Aeronautics and Space Administration (NNX13AI13G) and the Cancer Prevention and Research Institute of Texas (RP100644). This work was also supported by the Office of Medical Research, Departments of Veterans Affairs (RFS) and the National Institutes of Health (R01-DK63621, R01-CA134571 to RFS).

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Author notes

  1. L Li and V T Puliyappadamba: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    L Li, V T Puliyappadamba, S Chakraborty, A Rehman, V Vemireddy & A A Habib

  2. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    D Saha, S Burma & D A Boothman

  3. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    R F Souza

  4. Esophagal Diseases Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    R F Souza

  5. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    K J Hatanpaa & P Koduru

  6. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    D A Boothman

  7. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    D A Boothman & A A Habib

  8. VA North Texas Health Care System, Dallas, TX, USA

    A A Habib

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  1. L Li
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Correspondence to A A Habib.

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Li, L., Puliyappadamba, V., Chakraborty, S. et al. EGFR wild type antagonizes EGFRvIII-mediated activation of Met in glioblastoma. Oncogene 34, 129–134 (2015). https://doi.org/10.1038/onc.2013.534

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  • DOI: https://doi.org/10.1038/onc.2013.534

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